Signaling mechanism of PMA-induced differentiation of K562 cells.

We have studied the signaling pathways responsible for the monocytic and/or megakaryocytic differentiation of K562 cells. The results demonstrated that although the mitogen-activated protein kinase (MAPK) was activated during the phorbol myristate acetate (PMA)-induced monocytic and/or megakaryocytic differentiation of K562 cells, the overexpression of Ha-ras which can activate the MAPK did not induce the monocytic and/or megakaryocytic differentiation of K562 cells. Instead PMA-induced megakaryocytic differentiation of K562 cells was inhibited by the pretreatment of pyrrolidine dithiocarbamate, a specific nuclear factor kappaB (NF-kappaB) inhibitor. Taken together, these results suggest that the activation of NF-kappaB rather than that of MAPK might be involved in the PMA-induced megakaryocytic differentiation of K562 cells.